Continuous cuprizone intoxication allows active experimental autoimmune encephalomyelitis induction in C57BL/6 mice

• Published in: Histochemistry and cell biology Vol. 152; no. 2; pp. 119 - 131
• Main Authors: Yakimov, Vladislav, Schweiger, Felix, Zhan, Jiangshan, Behrangi, Newshan, Horn, Anja, Schmitz, Christoph, Hochstrasser, Tanja, Kipp, Markus
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-08-2019; Springer Nature B.V
• Subjects: Animal models; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; CD3 antigen; Cell Biology; Cuprizone; Degeneration; Developmental Biology; Experimental allergic encephalomyelitis; Forebrain; Immunization; Inflammation; Intoxication; Leukocytes (granulocytic); Lymphocytes; Metabolism; Microglia; Mimicry; Multiple sclerosis; Myelin; Oligodendrocyte-myelin glycoprotein; Oligodendrocytes; Original Paper; Oligodendrocyte injury; Neuroinflammation; Peripheral immune-cell recruitment; Multiple sclerosis
• ISSN: 0948-6143; 1432-119X
• DOI: 10.1007/s00418-019-01786-4

Oligodendrocyte degeneration is a hallmark of multiple sclerosis pathology, and protecting oligodendrocytes and myelin is likely to be of clinical relevance. Traditionally, oligodendrocyte and myelin degeneration are viewed as a direct consequence of an inflammatory attack, but metabolic defects might be equally important. Appropriate animal models to study the interplay of inflammation and metabolic injury are, therefore, needed. Here, we describe that in spite of its immunosuppressive effects, a continuous intoxication with cuprizone allows the induction of active experimental autoimmune encephalomyelitis (EAE) by myelin oligodendrocyte glycoprotein (MOG
35–55
) immunization. Although the clinical severity of EAE is ameliorated in cuprizone-intoxicated mice, the recruitment of granulocytes, and especially, CD3
+
lymphocytes into the forebrain is triggered by the cuprizone insult. Such combined lesions are further characterized by oligodendrocyte apoptosis and microglia activation, closely mimicking type III multiple sclerosis lesions. In summary, we provide a protocol that allows to study the direct interplay of immune-mediated and metabolic oligodendrocyte injury and its consequences for the cerebral white and grey matters.